UniProt: P54803 (GALC_HUMAN); HGNC:4115; EC 3.2.1.46; gene on chr14.
Glycosyl hydrolase family GH59 (CAZy GH59; Pfam PF02057).
GALC is a lysosomal glycosidase of glycosphingolipid catabolism. It hydrolyses the
terminal galactose from galactosylceramide (galactocerebroside) to yield ceramide +
D-galactose (EC 3.2.1.46, RHEA:14297), and also hydrolyses galactosylsphingosine
(psychosine) and other galactolipids.
Requires saposin A (SapA, from PSAP) for lipid presentation. GALC-SapA crystal
structure (murine) = 2:2 heterotetramer; open channel from GALC active site to SapA
hydrophobic cavity presents the polar glycosyl headgroup to the active site while shielding
the acyl chains. "This enzyme requires the saposin SapA for lipid processing and defects in
either of these proteins causes a severe neurodegenerative disorder, Krabbe disease"
PMID:29323104. Active-site residues (UniProt): proton donor/acceptor His... actually
ACT_SITE 198 (proton donor/acceptor), 274 (nucleophile). GH59 retaining glycosidase.
Lysosome / lysosomal lumen. GO IC annotations place it in endolysosome lumen (GO:0036021),
inferred from the general finding that endolysosomes are the principal sites of acid
hydrolase activity PMID:27498570 combined with GALC's acid-hydrolase MF (GO:0004336).
PMID:27498570 is a general endolysosome study and does NOT mention GALC by name; the
endolysosome-lumen call is a curator inference (IC). Lysosome localization is well
established (subcellular location "Lysosome"; typical acid hydrolase, mannose-6-phosphate
pathway implied).
Deficiency causes Krabbe disease / globoid cell leukodystrophy (KRB; MIM:245200),
autosomal recessive. Psychosine (galactosylsphingosine) accumulation is neurotoxic and
drives demyelination. Many pathogenic missense variants across the gene (UniProt lists
dozens of KRB variants). Four clinical forms; infantile form ~90% of cases.
GOA MF term present and current: GO:0004336 galactosylceramidase activity (verified via
OLS, not obsolete). This is the core MF used in core_functions.
Core BP: GO:0006683 galactosylceramide catabolic process (verified current).
Locations: GO:0005764 lysosome, GO:0043202 lysosomal lumen (both verified current).
Notes on individual annotations:
- PMID:15657896 is a review on GALC in cancer, annotated IDA to GO:0006683. IDA on a
review is unusual, but it does correctly describe GALC degrading galactosylcerebroside to
ceramide. Not a core-defining primary experiment; keep as non-core / accept the biology
but flag the evidence type. Per policy do NOT REMOVE (can't see full curator context) —
accept the biology, note the review nature.
- GO:0030149 sphingolipid catabolic process (IDA, PMID:8281145): broader parent-type BP;
GALC does act in sphingolipid catabolism (galactosylceramide is a glycosphingolipid).
Keep as non-core (galactosylceramide catabolic process is the precise term).
- GO:0046479 glycosphingolipid catabolic process (TAS, Reactome): correct, broader than the
precise galactosylceramide catabolic process; keep as non-core.
- Reactome/GO_REF/IEA/ISS/IBA MF and BP annotations all consistent; accept.
Falcon deep research is OUT OF CREDITS (HTTP 402) — no -deep-research-falcon.md generated.
Review grounded in GALC-uniprot.txt, GALC-goa.tsv, and cached publications/PMID_*.md.
The preceding text is an unchanged historical journal. Its older numerical kinetic statements and quote-to-claim associations are not automatically adopted. The current source guide records what was actually read and the review YAML contains the present judgments.
Positive human purification and COS-1 expression support GALC's defining galactosylceramidase function. Cat RNA in the cloning workflow was only a probe intermediate. Full original assay Methods were not recovered, so numerical pH/Km details are omitted from current reasons (PMID:8281145(https://pubmed.ncbi.nlm.nih.gov/8281145/), PMID:8399327(https://pubmed.ncbi.nlm.nih.gov/8399327/)). The human gene paper supports established lysosomal hydrolysis as background; it is not a direct imaging assay (PMID:7601472(https://pubmed.ncbi.nlm.nih.gov/7601472/)).
Selected GALC-SapA original text supports an acidic-compartment lipid-presentation mechanism. The principal structure uses mouse proteins, with a separate limited human pull-down; substrate placement is modeled rather than resolved in that complex. General hydrolase-active endolysosome physiology supports the IC location without pretending that GALC itself was imaged. A single precise endolysosome-lumen core avoids repeating its ancestor compartment (PMID:29323104(https://pubmed.ncbi.nlm.nih.gov/29323104/), PMID:27498570(https://pubmed.ncbi.nlm.nih.gov/27498570/)).
All 20 current contexts are retained. The 19-row parser forecast collapses the unextended activity assertion and a separately assigned three-atom substrate/product context. The planned twentieth row restores that existing context, not a new assertion, and leaves the unextended row intact. The original two assignments, literal conjunction and old mapping ambiguity remain explicit. The current InterPro reference differs from an older combined-inference reference; both are preserved in their respective versions.
The three actual IBA placements descend from the verified ancestral node. Mouse donor papers provide positive cDNA-expression and mutant biochemical grounding, with abstract-only access limits retained; a donor's title foregrounding SapA does not demonstrate a curator error (PMID:8769874(https://pubmed.ncbi.nlm.nih.gov/8769874/), PMID:11371512(https://pubmed.ncbi.nlm.nih.gov/11371512/), PMID:11734583(https://pubmed.ncbi.nlm.nih.gov/11734583/)). The primary catalytic and pathway claims remain independently supported in human.
The current four products have exact official sequences of 685, 662, 659 and 589 residues. Sequence verification does not prove equivalent activity or trafficking. Historical 669-residue cDNAs, alternative initiation and protein fragments are not silently assigned current suffixes (PMID:8297359(https://pubmed.ncbi.nlm.nih.gov/8297359/), PMID:9434153(https://pubmed.ncbi.nlm.nih.gov/9434153/)). Variant-expression studies corroborate activity sensitivity but do not create extra biological processes or product equivalence.
Two source inconsistencies are explicitly recorded: Reactome's modeled glucose output disagrees with the same reaction's galactose definition, and UniProt's ester-bond phrase disagrees with glycosidic chemistry. The model's human GALC identity and lumen assignment remain verified; all fetched source bytes are preserved. Eight current excerpt occurrences are checked against retained source bytes. All 30 inherited associations remain historical provenance. No NEW annotation, provider report or canonical acquisition has been generated during this private review. Genuine native acquisition, context restoration and targeted validation remain future work.
The authorized existing lane refreshed GALC with the native no-seed command while preserving the inherited review. All 20 original contexts and every field of the 16-column export matched the retained current records. Fourteen normal sources were reused unchanged and 19 missing publications were acquired, completing the 33-source union. The genuine native 19-row seed is preserved separately without edits. Its collapsed activity pair is represented here as two original contexts: raw3 remains unextended at review1; raw4 is restored at review19 with its exact substrate/two-product conjunction. This is source-context restoration, not a NEW annotation. Explicit joins supplement the strict matcher, which does not check assignedBy or extension identity.
All four native product declarations and sequences agree; source titles and availability flags were reconciled, and all eight current excerpts match the actual normal caches. PMID:20886637 and PMID:34449528 now have full caches, but their manual assessments retain the actual abstract reading scope. PMID:8940268 remains abstract-only after failed publisher-restricted XML/HTML/PDF fallbacks. The 20 approved judgments, one core, 36 manual assessments, two source defects and all 30 historical quotation associations remain intact. Native EDIT history and targeted validation follow.
Native validation passed with zero advisories; strict GOA matching passed, and computed status is COMPLETE for all 20 reviewed original contexts. No NEW annotation was added. The first validation diagnostic is preserved: three extension predicates initially used descriptive objects, while the schema requires CURIE strings. Only those wrappers were projected to their exact RO identifiers; labels and the literal source conjunction remain in the archive. All 33 scientific source files remain unchanged. The initial INITIALIZED-versus-COMPLETE status diagnostic is retained. Native EDIT history, private rendering/link checks and scoped whitespace checks accompany this candidate.
The explicit root-organelle policy includes lysosome and prohibits replacing a supported organelle claim with a subcompartment. The three lysosome rows (IBA, UniProt location mapping and TAS) are therefore retained as ACCEPT. Their source-specific evidence remains unchanged. The IBA placement is sound, so the previous granularity-failure classification is withdrawn. Existing lysosomal-lumen and endolysosome-lumen annotations, the precise core location, all original contexts and the eight current excerpts remain intact. This corrects the policy application in the preceding dated review; the earlier journal and history remain unchanged. The current tally is 18 ACCEPT and two MODIFY, with the latter confined to broad catabolic-process refinements. Target validation passed with zero advisories, strict GOA matching passed for all 20 original contexts, and computed status remains COMPLETE. A genuine new EDIT history, private rendering/link checks and scoped whitespace checks passed; all 33 scientific sources and the complete context/evidence archive remain unchanged.
The earlier two process refinements are superseded: both broad sphingolipid and glycosphingolipid catabolism are retained because the curated human record covers both GalCer and psychosine hydrolysis (UniProt P54803, CC:CATALYTIC ACTIVITY, RHEA:14297 and RHEA:43908; PMID:8399327). Production GO-CAM 696022cd00002259 explicitly includes the GALC activity under sphingolipid catabolism with PMID:8281145. Its deliberate context is now acknowledged, and the independent second substrate supplies the reason the broader terms remain informative. The GalCer-specific MF core is not relabeled as psychosine activity; an expert/ontology question records that separate reaction.
The authentic original abstract remains the inspected scope for PMID:8399327. This does not invalidate curated UniProt kinetic and acid-pH evidence. The N-acyl substrate Km and pH optimum are now distinguished from original full-Methods verification, and a short record-section-labelled pH excerpt supports the acid-hydrolase setting. The FUNCTION chemistry defect is represented as WRONG_STATEMENT/CHECK with its full sentence, preserving all source bytes. Reader-facing identifiers and spacing were corrected; no historical journal or history record was rewritten.
The source archive now exposes the exact GO-CAM activity and retains all 20 originals, the separate restored three-atom context, four sequences and 30 historical quotation associations. Current support has nine excerpt occurrences; the additional full UniProt sentence is counted separately in the same source quotation budget. Target validation passed with zero advisories, strict GOA matching passed for all 20 original contexts, and computed status remains COMPLETE. The genuine EDIT history, private render/link checks and scoped whitespace checks passed. All 33 scientific sources and every original machine context remain unchanged. The first follow-up check caught a scalar record_section where the schema requires a list; the scalar was normalized to a one-item list, then the string was explicitly quoted for YAML parser compatibility. Both diagnostics are preserved. The pH wording, source and scientific judgments did not change.
Both broad catabolism assertions remain ACCEPT. Their explicit supporting-reference links now identify the same UniProt CC:CATALYTIC ACTIVITY block, with the complete RHEA:43908 psychosine reaction quoted once in that reference’s structured finding. The Reactome glycosphingolipid row again explains its own pathway-to-GALC catalyst chain. The separate source-output discrepancy remains recorded. The GalCer molecular core is now a concise biological statement of acid-compartment hydrolysis with saposin A-assisted substrate access; term-selection and inspected-source limits remain in this journal and the source guide. UniProt; Reactome pathway
The native section-backfill helper located the reaction excerpt in CC:CATALYTIC ACTIVITY. Its ten words plus the complete fourteen-word FUNCTION defect sentence total 24 words from the record. The optional four-word pH excerpt is retired; its accurate curated value and citation remain, and the prior literal association is preserved at commit 07cc51e. The current total remains nine quote occurrences. All 30 older associations remain historical provenance.
A fresh official QuickGO query returns the direct GO:0036021 is_a GO:0043202 edge; its complete small response, date, URL and hash are retained in the source-evidence file. The precise core location and the three accepted lysosome annotations therefore remain unchanged. The chemistry correction now consistently says glycosidic bonds. The reference note describes the two preserved activity-source contexts in ordinary language.
All 20 annotation actions and original machine contexts, three extension atoms, four products, core terms, 33 scientific sources and earlier history remain unchanged. Target validation passed with zero curation advisories, strict GOA matching passed for all 20 original contexts, and computed status remains COMPLETE. The genuine EDIT history, private render/link checks and scoped whitespace checks passed. All 33 scientific source bytes and the derived term caches remain unchanged.
The acid-pH anchor is restored beside the core location support. The complete psychosine equation remains quoted once in the UniProt reference finding, unfolded using the repository’s normal source rendering. The two broad-process links still cite that finding but no longer label a section without quoting it. The separate activity context is explained by its actual substrate/product conjunction; source-reading limits remain in the reference assessment and guide. These changes preserve all 20 ACCEPT decisions, original contexts, three extension atoms, four products and the full source discrepancies. The current review has ten excerpt occurrences.
The related in-repository pathway module derives its GALC step from this review and Reactome; it is linked as context, not independent primary evidence. All 33 scientific source files and earlier journal/history remain unchanged. Target validation passed with zero curation advisories, strict GOA matching passed for all 20 original contexts, and computed status remains COMPLETE. The genuine EDIT history, private render/link checks and scoped whitespace checks passed. All 33 scientific source bytes and the derived term caches remain unchanged.